In most physical, chemical and biological processes result in a change in the heat content of the system. Calorimetry is the methodology to directly measure changes in heat content. Calorimetric instruments are used in widespread application in physics, chemistry and biology. From calorimetric data fundamental thermodynamic properties such as internal enthalpy change, ΔH, heat capacity change, ΔCp, and absolute heat capacity, Cp, can be obtained. Further analysis of data can indirectly give other thermodynamic properties such as Gibbs free energy change, ΔG°, and entropy change, ΔS°. For more complex systems calorimetric instruments are used for monitoring thermal events as an indicator of complex or unknown processes occurring in the samples.
There are mainly two commercial calorimetric methodologies—isothermal calorimetry and scanning calorimetry. Scanning calorimetry means that the temperature of the calorimetric device is actively changed, while for isothermal calorimetry the temperature is nearly constant or changed by the heat adsorbed or produced by the process in the calorimeter.
Due to sample specific needs or methodological reasons the commercial calorimetric available instruments are more or less specialized for specific areas of interest in physics, chemistry and biology. There are for example differential scanning calorimeters (DSC) that are specialized for solid samples and others for liquid solutions or mixtures. There are calorimeters designed for use at low, high temperature applications as well as in the temperature rang 0-120° C. There are instruments designed for solely titration at isothermal conditions (ITC).
Presently, industrial calorimetric applications are mainly related to material science issues regarding manufacturing control and physical or chemical stability of products. Biological processes are often connected with changes in metabolic activity, which are manifested by changes in heat as a result from oxidative processes on cellular level. The type of biological material that have been studied by isothermal calorimetry are for example mammalian cells, plant cells, prokaryotic cells, mammalian tissues, plant tissues and whole organisms. Examples on cellular events that have been studied by calorimetry are mitosis, necrosis, apoptosis, and induced changes in metabolic activity. The applications have potential to be applied biological industrial areas among others such as eukaryotic and prokaryotic protein production, drug discovery, drug development and clinical work (see e.g. Beezer, A. E., et al (1993) Microbios. 73, 205-213, Beezer, A. E. (1990) Tokai J Exp Clin Med. 15, 369-372, Monti, M. (1990 Thermochimica Acta 172, 53-60, and Takahashi, K. (1990) Tokai J Exp Clin Med. 15, 387-394). One important reason for this is that the methodology presents data as real-time data, which is a common demand on new technologies for biological applications.
All methods and technologies for the life science industrial organizations need to have high sample through put with simple sample handling. In order to satisfy industrial needs the methods have to be based upon parallel multiple sample detection, preferably as array system. The commercial calorimetric instruments that are available have that in common that the samples are individually loaded or inserted into the calorimeter. There are a few commercial available multi-channel calorimeters which all have individual calorimetric channels that share a common thermostat.
There is a number of multi-channel calorimeters described that either use resistance thermometry, i.e. temperature determination by thermistor resistor thermometer or platinum resistor thermometer, or thermal detection of electrothermal voltage determination, as described in patent publications US2004/0107986, US2005/0241869, US2005/0036536 and US2004/0038228. There are microcalorimeters described that are based on thermopile chips, se US2004/0038228 and Maskow, T. et al. (2006) J. Biotechnol. 122, 431-42. These types of instruments are characterized by high sensitivity, small sample volumes (a few micro liters), fast response, and appearing to be suitable for multi-channel designs. However, in many applications the sample volumes are too small, e.g. in experiments with a monolayer of cells, for non-homogenous samples like soil and with samples like tissues, organs and animals. Further, for heat conduction calorimeters the detection limit for a certain type of sample is proportional to the amount of material contained in the vessel. For materials with very low specific thermal powers it may therefore be necessary to conduct the measurements with sample volumes much larger than a few micro liters. There are security demands and cost effectiveness demands from industrial users that the samples are contained in and experiments performed in disposable sample containers. The chip technology has not yet been able to handle this problem.
Thermopile heat-conduction calorimeters can be used for measuring high sensitivity changes in heat content from samples in which physical, chemical or biological processes occur. The heat is measured by measuring the heat flow from a sample, through a thermopile, to a thermostated heat sink. This principle of measuring heat has not yet been shown to be compatible with multiple removable, and therefore disposable, multiple sample vessels in array format. The reasons for this have been difficulties in (i) ensuring good thermal equilibration of the inserted body of an array when inserting an array into the measuring chamber, (ii) avoiding dramatic thermal and mechanical, i.e. pressure, disturbances of thermostating blocks and heat-sink when inserting an array into the measuring chamber, and (iii) ensuring high thermal conductivity connection between a removable array of multiple vessels and heat-flow sensors, such as thermopiles. Regardless if it is a single vessel container or an array of multiple vessel containers, the sample container needs to be introduced into the calorimetric measuring chamber in more than one step in order to obtain thermal equilibrium and stable calorimetric signal within sufficient time. The calorimetric sample vessels are vertically inserted into calorimetric devices. For an array of multiple vessel containers this way of insertion causes poor and long equilibration time thermal equilibration. It also causes large disturbances of the thermopiles, due to piezoelectric response of the thermopiles.
Accordingly, there is a need for a calorimetric instrument that is based upon an array system where the sample containers are disposable. The instrument should be simple to handle and with high sensitivity according to the demands of the users.